Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones

Craniosynostosis (CS) is a common malformation occurring in ~4 per 10,000 live births in
which the sutures between skull bones close too early, causing long-term problems with brain
and skull growth. Infants with CS typically require extensive surgical treatment and may
experience many perioperative complications, including hemorrhage and re-synostosis. Even
with successful surgery, children can experience developmental and learning disabilities or
vision problems. Most often, CS appears as isolated nonsyndromic CS (NSC). Of the several
subtypes of CS, unilateral or bilateral fusion of the coronal suture is the second most
common form of CS accounting for 20-30% of all NSC cases. The etiology of coronal NSC (cNSC)
is not well understood, although the published literature suggests that it is a
multifactorial condition. About 5-14% of coronal craniosynostosis patients have a positive
family history, with a specific genetic etiology identified in >25% of cNSC cases, suggesting
a strong genetic component in the pathogenesis of this birth defect. The causes for cNSC and
its phenotypic heterogeneity remain largely unknown. An international team of investigators
will generate large genomic and gene expression datasets on samples from patients with cNSC.
State-of-the-art imaging, genetic, and developmental and systems biology approaches will be
used to quantitatively model novel pathways and networks involved in the development of cNSC.
Novel variant-, gene- and network-level analyses will be performed on the genomic data
obtained from cNSC cases, their relatives, and controls to identify novel variants and
genetic regions associated with cNCS. Quantitative, analytical, and functional validations of
these predictions will provide insights into the etiology and possible therapeutic targets
for CS and potentially other bone-related disorders.